The DNA in each normal human cell is virtually identical. The key to cellular differentiation therefore lies in understanding the gene products—transcripts and proteins—that are derived from the genome. For more than a decade, it has been possible to measure the levels of transcripts in a cell at the whole genome level (1). The word “transcriptome” was coined to denote this genome-wide assessment (2). However, it has been difficult to determine which of the two strands of the chromosome (Plus or Minus) serves as template for transcripts in a global fashion. Sense transcripts of protein-encoding genes produce functional proteins while antisense transcripts are often thought to have a regulatory role (3-7).
Several unequivocal examples of antisense transcripts, such as those corresponding to imprinted genes, have been described (reviewed in (3-7)). However, estimates of the fraction of genes associated with antisense transcripts in mammalian cells vary from less than 2% to more than 70% of the total genes (8-18). There is a continuing need in the art to identify expression regulatory mechanisms and agents useful for regulating expression.